Is CPT2 p.Ser113Leu (c.338C>T) pathogenic?

CPT2 p.Ser113Leu (c.338C>T) is classified Pathogenic/Likely pathogenic in CPT2 (ClinVar, Multiple submitters, 54 submitters; last evaluated 2026-06-22). AlphaMissense: ambiguous (0.4283); Rare (popmax 0.186%, nfe); Associated with CPT2-related disorder.

How common is CPT2 p.Ser113Leu (c.338C>T) in the general population?

CPT2 p.Ser113Leu (c.338C>T) is rare (popmax 0.186%, nfe) (gnomAD).

What do computational predictors say about CPT2 p.Ser113Leu (c.338C>T)?

AlphaMissense predicts ambiguous (score 0.4283) — an in-silico prediction, not a clinical call.

CPT2 p.Ser113Leu

Q: What condition is associated with CPT2 p.Ser113Leu (c.338C>T)?

CPT2 p.Ser113Leu (c.338C>T) is associated with CPT2-related disorder, carnitine palmitoyl transferase II deficiency, myopathic form, carnitine palmitoyl transferase II deficiency, severe infantile form (ClinVar).

c.338C>T · rs74315294 · VCV8953

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 54 submitters

AlphaMissense

ambiguous

0.4283 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.186%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

CPT2-related disorder

Computational evidence

Protein change
AlphaMissense	0.4283	ambiguous
REVEL	0.887	moderately pathogenic-leaning
SaProt	LLR -13.35	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 17 kb · p 0.062 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.186% European (non-Finnish) · 2,197/1,178,070 alleles

Filtering AF 0.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.177%

Overall 0.167% 2,697/1,611,988 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.923%	108
European (non-Finnish)grpmax	0.186%	536
Remaining individualsnot grpmax-eligible	0.162%	618
Admixed American	0.08%	1,250
Middle Eastern	0.066%	1,514
African / African-American	0.0333%	3,000
East Asian	0.029%	3,452
South Asian	0.0286%	3,500
Finnishnot grpmax-eligible	0.0156%	6,402

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CPT2
Protein: p.Ser113Leu
Coding: c.338C>T
MANE Select: NM_000098
dbSNP: rs74315294
Type: single nucleotide variant
Location: chr1:53202427 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.52
Residue 113: a UniProt-annotated variant site (in cpt2d; muscular form; frequent mutation)

Full CPT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CPT2-related disorder

Also linked: carnitine palmitoyl transferase II deficiency, myopathic form carnitine palmitoyl transferase II deficiency, severe infantile form carnitine palmitoyl transferase II deficiency, neonatal form encephalopathy, acute, infection-induced, susceptibility to, 4 carnitine palmitoyltransferase II deficiency

Similar variants

CPT2 p.Ser113= Uncertain significance ★★ same residue
CPT2 c.340+1G>C Pathogenic/Likely pathogenic ★★ same condition
CPT2 c.340+5G>A Likely pathogenic ★★ same condition
CPT2 c.341-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Ala67Gly Likely pathogenic ★★ ⚠ same condition
CPT2 p.Arg124Gln Likely pathogenic ★★ ⚠ same condition
CPT2 p.Arg124Ter Pathogenic/Likely pathogenic ★★ same condition
CPT2 p.Arg151Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cpt2-p-ser113leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown